Project Summary/Abstract Age-related declines on many cognitive abilities are well documented and are highly associated with subsequent development of Alzheimer?s disease (AD). Nevertheless, there is great variability in cognitive abilities across individuals in susceptibility to these age-related changes. It may help to identify potential preventive measures by elucidating the mechanisms underlying this variability. Recent advances in cognitive neuroscience suggests that, among the elderly, variation in cognition might be due to the differences in present brain reserve [a combined result from peak brain reserve (peak BR; peak neurobiological capital at young age) and the brain maintenance (BM; ability of maintain against aging-related morphologic brain decline or pathological accumulation over time)] and cognitive reserve (CR; the extent of cognitive function exceeding what can be expected from a certain level of brain aging or pathology). Adherence to the Mediterranean-type diet (MeDi) is one of the top modifiable protective factors against AD and cognitive decline in the literature. However, which of the three reserve concepts (BR, BM, and CR) play a role in the cognitive benefits of MeDi is unclear. Obtaining insight into the role of the reserve concepts in the context of diet and AD or cognition will assist to prioritize public health efforts and provide a firm foundation for dietary recommendations on cognitive resilience and AD prevention. We aim to examine the respective roles of BR, BM and CR in cognitive benefits of MeDi, using data from a unique research population which includes 562 cognitively healthy participants aged 20-80, evaluated with multimodal brain imaging measures, a neuropsychological battery, and questionnaires on many demographic and lifestyle factors. Five-year follow-up of the cohort is ongoing. Thus, we are well positioned to explore the association between MeDi and present BR in all age groups, of particular interest will be the present BR of young adults representing the peak BR. For BM, we have previously developed relative BM measures using cross-sectional data. More importantly, the longitudinal data will allow us to directly measure BM. Finally, we have extensive experience in CR quantification. Specifically, we will: 1) Examine whether healthy diet such as MeDi is associated with larger BR. We will examine whether closer adherence to MeDi is associated with larger BR in all age groups, with the association in the young adults approximating the association of MeDi with Peak BR. 2) Examine whether MeDi is associated with BM. We will examine whether MeDi is positively associated with a relative BM proxy using cross-sectional data, and with a direct measure of BM (using longitudinal change of brain measures). 3) Examine whether MeDi is associated with CR. Using cross-sectional data, we will examine whether MeDi is associated with a ?residual? estimate of CR, or with the expression of previously identified CR-brain networks. Using longitudinal data, we will examine whether MeDi moderates the relationship between brain and cognitive change.